GLYCINE POTENTIATES THE NMDA RESPONSE IN CULTURED MOUSE-BRAIN NEURONS
GLYCINE POTENTIATES THE NMDA RESPONSE IN CULTURED MOUSE-BRAIN NEURONS
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DOI：
10.1038/325529a0
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发表时间：
1987-02-05
期刊：
影响因子：
64.8
通讯作者：
ASCHER, P
中科院分区：
文献类型：
--
作者：
JOHNSON, JW;ASCHER, P
脊椎动物中枢神经系统中介导“快速”突触过程的递质通常分为两个不同的类别，据信它们在受体水平上不表现出相互作用。 “抑制性递质”（如甘氨酸和 GABA）被认为仅作用于介导氯离子电导增加的受体，而“兴奋性递质”（如 L-谷氨酸）被认为可激活介导阳离子电导增加的受体1。最著名的兴奋性受体是由 N-甲基-D-天冬氨酸 (NMDA)2 特异性激活的受体，最近在单通道水平上对其进行了表征3-5。 NMDA 激动剂激活的反应是独特的，因为它表现出电压依赖性 Mg 阻滞3,6。我们在此报告，这种反应表现出另一个显着的特性：它被甘氨酸显着增强。这种增强作用不是由抑制性士的宁敏感的甘氨酸受体 7,8 介导的，并且在甘氨酸浓度低至 10 nM 时即可检测到。在由 NMDA 激动剂激活的通道打开频率增加的情况下，可以在outside-out贴片中观察到这种增强作用。因此，除了作为抑制性递质的作用外，甘氨酸还可以通过 NMDA 受体的变构激活促进大脑中的兴奋性传递。
Transmitters mediating 'fast' synaptic processes in the vertebrate central nervous system are commonly placed in two separate categories that are believed to exhibit no interaction at the receptor level. The 'inhibitory transmitters' (such as glycine and GABA) are considered to act only on receptors mediating a chloride conductance increase, whereas 'excitatory transmitters' (such asL-glutamate) are considered to activate receptors mediating a cationic conductance increase1. The best known excitatory receptor is that specifically activated byN-methyl-D-aspartate (NMDA)2which has recently been characterized at the single channel level3–5. The response activated by NMDA agonists is unique in that it exhibits a voltage-dependent Mg block3,6. We report here that this response exhibits another remarkable property: it is dramatically potentiated by glycine. This potentiation is not mediated by the inhibitory strychnine-sensitive glycine receptor7,8, and is detected at a glycine concentration as low as 10 nM. The potentiation can be observed in outside-out patches as an increase in the frequency of opening of the channels activated by NMDA agonists. Thus, in addition to its role as an inhibitory transmitter, glycine may facilitate excitatory transmission in the brain through an allosteric9activation of the NMDA receptor.